tbuckley/cabot-search huggingface dataset:
Efficacy and safety of cosibelimab, an anti–PD-L1 antibody, in patients with metastatic cutaneous squamous cell carcinoma.
Authors: Philip R. Clingan, Daniel Brungs, Susan Arnold, Jermaine Coward, Samuel J. Fourie, Dean Laurence Harris, Andrii Kurochkin, Rahul Ladwa, Niel Malan, Andrew Michael Mant, Margie McGrath, Vinay Sharma, Hong Shue, Andrea Tazbirkova, James Oliviero, Jayesh Desai
Journal: Journal of Clinical Oncology (2022)

9537 Background: Programmed death receptor-1 (PD-1)–blocking antibodies are approved as monotherapy treatment for patients (pts) with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or radiation. Cosibelimab is a high-affinity, fully human programmed death ligand-1 (PD-L1)–blocking antibody with a functional Fc domain capable of inducing antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against tumor cells. Study CK-301-101 (NCT03212404) is a global, multicenter, multicohort, pivotal trial that enrolled pts with select advanced cancers for treatment with cosibelimab. Here we present the primary analysis of the registration-enabling expansion cohort in pts with metastatic CSCC. Methods: Adult pts with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 who had metastatic (nodal and/or distant) CSCC not amenable to local therapy were eligible to participate. Cosibelimab was administered as a fixed dose of 800 mg every 2 weeks (Q2W) intravenously. The primary endpoint was confirmed objective response rate (ORR; complete response [CR] + partial response [PR]) assessed by independent central review according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and the key secondary endpoint was duration of response. Results: Seventy-eight pts with metastatic CSCC were treated with cosibelimab and comprise the efficacy and safety populations (59M/19F; median age: 71 years). The confirmed ORR was 47.4% (95% CI: 36.0, 59.1; 6 CRs and 31 PRs) and the median duration of response was not reached at the time of data cutoff (median duration of follow-up: 15.2 months), with 76% of responses ongoing (range: 1.4-31.8+ months). The Kaplan–Meier estimated probability of maintaining a response at 6 and 24 months was 88.1% and 72.5%, respectively. Treatment-related adverse events (TRAEs) were reported in 54 pts (69.2%); 7 pts (9.0%) experienced at least 1 grade 3 TRAE (no grade 4 or grade 5 TRAEs were reported) with the most common being increased serum lipase in 2 pts. Conclusions: Treatment with cosibelimab monotherapy resulted in a robust ORR with durable responses and demonstrated a predictable and manageable safety profile in pts with metastatic CSCC, supporting its use in the treatment of this cancer. Clinical trial information: NCT03212404.
Cost differential of costly cancer therapies by site of care.
Authors: Prem R. Warde, Christopher Junk, William Cavers, Elisea Avalos-Reyes, Kjel Andrew Johnson
Journal: Journal of Clinical Oncology (2022)

e18824 Background: In the past decade, oncology site of care (SOC) for drug infusions has shifted from physicians’ offices to hospital outpatient settings. This shift has raised questions regarding the potential impact of SOC on the value of cancer care. The purpose of this study is to explore current potential cost savings among select infused cancer therapies in stable patients transitioning from an outpatient setting to an office setting. Methods: We identified patients with cancer receiving a check-point inhibitor using medical claims data from June 30, 2018, to June 30, 2021, at a large national commercial insurer. We defined a non-stable patient as a patient who had yet to receive treatment for 180 days and/or may not be clinically stable to transition. A stable patient was defined as having received 180 days of treatment and further divided into either the “stable outpatient,” “stable office,” or “ineligible” group. Stable outpatient was defined as having the first, 6 month and last SOC in an outpatient setting. Stable office was defined as having the first, 6 month and last SOC in an office setting. Ineligible patients included those patients moving between the outpatient and office setting during the study period. We compared the stable outpatient and stable office groups using a t-test and simulated the potential savings of moving stable patients from the outpatient setting to the office, adjusting for drug, insurance type and state. Results: This study included 2,727 patients, of which 511 (18.7%) were stable. Of this stable population, the majority were outpatient 311 (60.9%) and 178 (34.8%) were office; 22 (4.3%) were ineligible. We examined the cost differences of select infusion drugs between the stable outpatient and stable office settings and observed significant cost differences across all drugs (p &lt; 0.01). Based on our observations, 83 (27%) stable outpatient patients are expected to transition to stable office patients during the study period. After adjusting for drug, insurance type and state, transitioning these patients would be $71,169 ($55,259 to $81,709) less costly per patient per year. Conclusions: Our results suggest significant cost savings by transitioning stable outpatient patients to the office setting. Encouraging stable patients to transition from the outpatient setting to the office setting may improve the value of cancer care by reducing the unit cost of therapy, which is key to practices as value-based contracting expands.
Interim analysis of neoadjuvant chemoradiotherapy with sequential ipilimumab and nivolumab in rectal cancer (CHINOREC): A prospective randomized, open-label, multicenter, phase II clinical trial.
Authors: Johannes Laengle, Irene Kuehrer, Dietmar Pils, Anton Stift, Bela Teleky, Friedrich Herbst, Bernhard Dauser, Matthias Monschein, Peter Razek, Stefanie Haegele, Wolfgang Hulla, Matthias Biebl, Hans Geinitz, Andreas L. Petzer, Clemens Bitterman, Friedrich Laengle, Dietmar Tamandl, Joachim Widder, Rainer Schmid, Michael Bergmann
Journal: Journal of Clinical Oncology (2022)

e15604 Background: Immune checkpoint inhibitors (ICI) do not seem to be effective in solid cancers, which lack an immunogenic priming. Radiotherapy (RT) can induce an immunogenic cell death (ICD) and thereby restore the susceptibility to ICI, especially in microsatellite stable (MSS) cancers. This study evaluates safety, tolerability and feasibility of neoadjuvant chemoradiotherapy (CRT) with concomitant ipilimumab (IPI) and nivolumab (NIVO) in locally advanced rectal cancer (LARC). Here we present the first requisite interim analysis. Methods: This is a prospective, randomized, open-label, multicenter, phase II investigator- initiated trial (IIT). Key eligibility criteria are patients with LARC and the medical need for a neoadjuvant CRT, without metastatic disease that is considered incurable by local therapies. In total 80 patients will be randomized (ratio 30:50) to receive either neoadjuvant CRT alone (50 Gy in 2 Gy fractions over 25 working days + concurrent capecitabine 1650 mg/m2/d PO) or in combination with a single dose of IPI 1 mg/kg IV at day 7, following 3 cycles of NIVO 3 mg/kg IV Q2W, starting on day 14. Patients undergo surgery within 10-12 weeks post CRT. The primary endpoint is safety of neoadjuvant CRT with sequential IPI and NIVO following surgical resection. Surgical complications are graded by the “Clavien-Dindo Classification” v2.0 and treatment-related adverse events (TRAEs) by the Common Terminology Criteria of Adverse Events (CTCAE) v5.0. Interim analyses for the surgical complication “reoperation” will be assessed after every 10th patient in the IPI/NIVO treatment arm. Reoperation numbers are compared to historically known and published ratios. If the observed case numbers are above the calculated upper 95% confidence interval (95% CIup), the study will be terminated. Results: From 06/2020-02/2022, 36 patients have been accrued, of whom 23 were randomized to the CRT+IPI/NIVO arm. Of these, the first 10 patients who underwent successful surgery were used for the present interim analysis. No patient experienced a surgical complication with the need for a reoperation (3Grade IIIb). Any surgical complication occurred in 8 (80%) patients, with the most common being Grade I (70%) and Grade II (50%) events. Conclusions: The addition of sequentially applied IPI and NIVO to neoadjuvant CRT does not increase the number of surgical reoperation rates. The study meets it’s interim analysis criteria to be safe to continue accrual. Clinical trial information: NCT04124601.
Mucormycosis in hematopoetic stem cell transplant recipients: A systematic review.
Authors: Mohammad Ebad Ur Rehman, Sajeel Saeed, Diana Franco, Asmi Chattaraj, Jawad Basit, Hamza Khan, Faizan Fazal, Faiz Anwer
Journal: Journal of Clinical Oncology (2022)

e19043 Background: Mucormycosis is a life-threatening infection caused by opportunistic fungi belonging to the order Mucorales. High mortality is reported in hematopoietic stem cell transplant (HSCT) recipients who develop mucormycosis in the post-transplant immunosuppressed state. This study reviews the epidemiology, diagnosis, treatment and outcome of mucormycosis in HSCT recipients. Methods: A systematic literature search was conducted on PubMed and Embase from inception to 5 Jan, 2022 using MeSH terms for 'mucormycosis' and 'hematopoietic stem cell transplantation'. We included case reports, case series and observational studies reporting individual patient data. Summary statistics were calculated for patient characteristics by tabulation and percentages. Hazard ratios were calculated using unconditional Cox proportional hazard models. Data analysis was done using SPSS. Results: The initial search revealed 405 articles. After exclusion of duplicates, reviews and non-relevant articles, data was included from 122 articles (183 patients). The most common sites of infection were lung (36.6%) and rhinocerebrum (7.1%). Disseminated infection occurred in 34 (18.6%) cases. Diagnosis was confirmed using histology, culture or both in 27%, 13% and 34% of cases, respectively. Seven genera of zygomycetes were identified, of which Rhizopus was most common (37.2%). The most common antifungals used were liposomal amphotericin B (LAMB) (74%) and posaconazole (27%). Surgical debridement was employed in 64 (35%) cases. Overall survival was 32% with LAMB and 34% with surgical debridement. Sixteen patients did not receive any therapy; none survived. Mortality was reported in 121 patients (68.4%). Death was attributed to mucormycosis in 84 cases (45.9%). Death attributed to mucormycosis was more frequent in Rhizopus infections (56%) compared to other species (40%, HR = 1.89, 95% CI 1.13-3.15, p &lt; 0.05). Patients who underwent HSCT due to chronic myeloid leukemia (CML) had greater mortality due to mucormycosis (72%) compared to those with other underlying diseases (43%, HR = 2.31, 95% CI 1.26-4.21, p &lt; 0.05). Conclusions: Mucormycosis has high mortality in HSCT recipients. Surgery and LAMB therapy can significantly improve survival. Prospective studies need to be undertaken to identify risk factors for mortality and appropriate treatment strategies. [Table: see text]
Chromosome 20q and 13q gain in metastatic colorectal cancer: Prognostic significance and genomic correlates.
Authors: Satish Maharaj, Radwa Sharaf, Rebecca A. Redman, Adam Rojan
Journal: Journal of Clinical Oncology (2022)

e15553 Background: Chromosome 13q and 20q gain are major molecular events in adenoma-carcinoma progression and metastasis. The prognostic significance and correlates of 13q and 20q gain in metastatic colorectal cancer (CRC) have not been established. Methods: A total of 108 cases were selected at the University of Louisville. We ran a custom research-use only algorithm to assess whole arm chr13q and chr20q gain from next generation sequencing data of CRC samples. The algorithm utilized the coverage data of baited regions of the genome to model the copy number of each segment. A gain call was made if &gt; 50% of the chromosome arm was gained. Tumors were noted as left-sided colon, right-sided colon, or rectal cancers. Data on demographics, treatment and Kaplan-Meier survival were analyzed. Results: The prevalence of 13q gain was 58% and 20q gain was detected in 61% of cases. Concurrent 13q and 20q gains were frequent, with 49% prevalence. The only 2 MSI-High samples were negative for 13q or 20q gain. Tumors with 13q and 20q gain were significantly more likely to have mutations in TP53 and APC (Table). Rectal tumors were significantly enriched for 13q gain ( p= 0.020) and 20q gain ( p= 0.007). Examining survival by tumor location, 13q gain conferred significantly worse outcome for rectal cancers ( p= 0.007), as did 20q gain ( p= 0.037). Conclusions: With median follow up of over 3 years, 13q and 20q gains were significantly associated with worse prognosis in rectal cancers. The data indicate that 13q/20q gain and associated molecular signature are important prognostic markers in CRC.[Table: see text]
The need for a personalized, comprehensive resource within the colorectal cancer community.
Authors: Kim Newcomer, Andrea Goodman, Negeen Fathi, Abdullah Shoeb
Journal: Journal of Clinical Oncology (2022)

e24139 Background: Colorectal cancer is the third-most commonly diagnosed cancer and the second-leading cause of cancer death in men and women combined in the United States. In efforts to manage the disease, patients and caregivers turn to a variety of tools and resources for financial assistance, information dissemination, emotional and peer support, and treatment planning, among other critical issues and needs they face. The Colorectal Cancer Alliance (the Alliance) is committed to providing patients and caregivers with a resource solution that encompasses all potential areas of need. Methods: A survey aimed at understanding needs, barriers, and quality improvement opportunity was disseminated via the Alliance's Blue Hope Nation community for two weeks and by email. One hundred sixty-seven colorectal cancer patients and forty caregivers of colorectal cancer patients completed the survey. Results: Patients and caregiver respondents alike report reliance on external tools and resources to manage disease and support information. Of the support methods, patient respondents reported using social media (46.11%); notebooks, journals, and planners (45.41%); online articles (44.91%); the Blue Hope Nation Facebook group (41.32%); cancer discussion boards (35.33%); and spiritual or religious advice (29.94%). Caregiver respondents reported relying on friends and family (57.5%); the Blue Hope Nation Facebook group (47.5%); healthcare websites (47.5%); the Alliance website (42.5%); and spiritual or religious advisors (37.5%). To minimize diagnosis-related stressors, patients reported they look for financial assistance, local peer support and groups, and mental health help. To provide more efficient care and limit stress, the community suggested the need for financial help, communication and support from other patients and caregivers, and informational resources. Conclusions: These survey results are consistent with other published learnings about patient and caregiver reliance on support tools and highlights the myriad resources that patients and caregivers currently use for managing colorectal cancer. The saturation of the market has compelled the Colorectal Cancer Alliance to create a one-stop-shop, personalized resource with tools to organize and effortlessly share customized information treatment plans, and other support mechanisms. Such patient and caregiver-directed resources may enable a better care experience and potentially lead to better physical and mental health outcomes for patients and their caregivers.
Evaluating the impact of perioperative antibiotic prophylaxis on the microbiome in patients with cutaneous malignancy.
Authors: Samuel Cass, Russell G. Witt, Xialong Meng, Pranoti Sahasrabhojane, Roland L. Bassett, Samuel Shelburne, Hsiu Yin Chang, Kinjal Somaiya, Kristi Mungovan, Sarah B. Fisher, Anthony Lucci, Jeffrey Edwin Lee, Merrick I. Ross, Jeffrey E. Gershenwald, Sheila Duncan, Nadim J. Ajami, Christina Lynn Roland, Jennifer Ann Wargo, Emily Zhi-Yun Keung
Journal: Journal of Clinical Oncology (2022)

TPS9602 Background: Preoperative antibiotic prophylaxis is commonly used to reduce surgical site infections (SSIs). However, the rate of SSIs following surgical procedures classified as clean is only 2-3%. Overuse of antibiotics is associated with several potential adverse effects, including dysregulation of the gut microbiome. Disruption of the composition and function of the native gut microbiota, referred to as dysbiosis, has been implicated in a number of inflammatory and autoimmune disorders, as well as gastrointestinal (GI) and non-GI cancers. Recent studies have demonstrated that antibiotics have a profound and persistent effect on the gut microbiota, as evidenced by diminished overall abundance and diversity, as well as alteration of community composition that includes a decreased relative abundance of bacteria in the Ruminococcaceae family. In melanoma, diversity of gut microbiota and relative abundance of Ruminococaceae have been linked to improved survival and enhanced response following immune checkpoint blockade. In this study, we seek to determine the impact of preoperative prophylactic antibiotic use on the gut microbiome in patients following surgery for stage I or II melanoma. Methods: In this non-comparative randomized pilot trial, the impact of prophylactic antibiotic use at the time of surgical intervention on gut microbiome diversity and composition will be studied. Patients diagnosed with clinical stage I or II melanoma undergoing wide excision with or without lymphatic mapping and sentinel lymph node biopsy are randomized 1:1 to either receive preoperative cefazolin or no preoperative antibiotics. Stool samples and peripheral blood are collected before surgery, the day of surgery (optional), on post-operative day 3 (optional), and 2 weeks and 3 months following surgery. The primary endpoint for the study is change in microbiome alpha diversity at 2 weeks following surgery. Secondary endpoints are change in relative abundance of microbes at 2 weeks and 3 months after surgery and SSI rates according to whether or not prophylactic antibiotics were administered at time of surgery. Exclusion criteria include recent antibiotic use (within 3 months), allergy to beta-lactam or cephalosporin antibiotics, increased risk of infection due to medical comorbidity or use of immunosuppressive medication. Enrollment began in October 2021. As of January 2022, 22 of 30 patients have been accrued to ensure complete sample collection for 20 patients. Study findings may inform a larger trial evaluating interventions to mitigate antibiotic impact. Clinical trial information: NCT04875728.
Racial disparities in receipt of curative surgery for early-stage non–small cell lung cancer in Florida.
Authors: Qinran Liu, Kamaria T. Jacobs, Gilberto Lopes, Clyde P. Brown, Paulo S. Pinheiro
Journal: Journal of Clinical Oncology (2022)

8539 Background: Lung cancer is the leading cause of cancer death in the United States. Receipt of curative-intent surgery for early-stage non–small cell lung cancer (NSCLC) is associated with disparities in race and socioeconomic status, which is subsequently related to the outcome of NSCLC. This study aimed to examine the racial disparity in receipt of curative-intent surgery among early-stage NSCLC in Florida. Methods: A total of 80,458 patients with early-stage NSCLC diagnosed from 2005 to 2017 were identified from the statewide cancer registry, Florida Cancer Data System (FCDS). Percentage of patients receiving curative-intent surgery was calculated for each race/ethnicity. FCDS data was linked to discharge data containing comorbidity information for each lung cancer patient. There was a 94% match between FCDS and discharge data. Multivariable logistic regression was used to determine the impact of race on receipt of curative-intent surgery for early-stage NSCLC. Results: Among 80,458 patients with early-stage NSCLC, 66,761 (83.0%) were White, 5,503 (6.8%) were Black and 6,981 (8.7%) were Hispanic. Of note, 69.5% Hispanic patients lived in South Florida. Asian patients (59.9%) had the highest proportion of curative surgery, followed by Hispanics (57.8%), Whites (52.9%) and Blacks (42.6%). In the multivariable model, patients with Charlson Comorbidity Index (CCI)≥3 had 34% lower odds of having curative surgery (OR, 0.66; 95% CI, 0.62 to 0.7) compared to patients who did not have any comorbidity (CCI=0). Highest poverty levels had 27% lower odds of receiving curative-intent surgery compared to lowest (OR: 0.73; 95% CI: 0.68 to 0.78). After adjusting for sociodemographic factors (i.e., age, sex, race, insurance, region) and clinical factors (i.e., histology, AJCC stage, CCI, smoking status), Blacks had 27% lower odds of receiving curative-intent surgery (OR, 0.73; 95% CI, 0.68 to 0.79), whereas Hispanics had 22% (OR, 1.22; 95% CI, 1.14 to 1.30) and Asians had 19% (OR, 1.19; 95% CI, 0.98 to 1.46) higher odds than Whites. In the stratified analysis by regions, Blacks had lower odds of receiving curative-intent surgery than Whites in all regions across Florida while Hispanics had higher odds of receiving surgery than Whites only in South Florida (OR, 1.29; 95% CI, 1.18 to 1.41). Conclusions: There are persistent racial disparities in receipt of curative-intent surgery for early-stage NSCLC in Florida. Specifically, Blacks are receiving less curative-intent surgery, despite adjustments for comorbidities, socio-economic status, and insurance. Ethno-regional differences within different regions of Florida are evident with Hispanics surpassing all other races in receipt of curative treatment in heavily Hispanic South Florida.
Evaluation of formulation-associated ifosfamide neurotoxicity.
Authors: Karin Abernathy, Colleen McCabe, Matthew Perciavalle, Manuel Cortez, Ryan Miller, Bradley Yelvington, Vicki Leigh Keedy, Elizabeth J. Davis
Journal: Journal of Clinical Oncology (2022)

e23562 Background: Ifosfamide, an alkylating agent used commonly in both hematologic and solid tumor malignancies, carries a notable risk for neurotoxicity/encephalopathy. Ifosfamide is available as both a reconstituted powder formulation and a solution for injection. Literature has shown that there may be higher rates of ifosfamide neurotoxicity/encephalopathy (INT/E) with the solution compared to the reconstituted powder. The primary objective of this study was to compare the rates of neurotoxicity/encephalopathy in association with the two available pharmaceutical formulations of ifosfamide. Methods: We performed a retrospective study of adult patients receiving at least one dose of either available pharmaceutical formulation of ifosfamide. The primary outcome was the incidence of formulation-associated INT/E. Secondary outcomes included additional risk factors for development of INT/E. Results: Of 218 patients evaluated, 212 were included in the study with 56 patients receiving the reconstituted powder formulation and 156 patients receiving the solution for injection formulation of ifosfamide. Baseline characteristics were similar between the two groups, including dose of ifosfamide received, use of INT/E prophylaxis, and renal and hepatic function. INT/E occurred in 4 patients (7.1%) receiving the reconstituted powder formulation vs 32 patients (20.5%) receiving the solution for injection (p = 0.022) Evaluation and analysis of additional risk factors for development of INT/E are ongoing, including the impact of baseline demographics, ifosfamide dosing, renal and hepatic function, and concomitant medications. Conclusions: In this study, hematology/oncology patients who were treated with ifosfamide had significantly lower rates of INT/E with the reconstituted powder formulation compared to the solution for injection. Further analysis regarding additional risk factors for INT/E development is ongoing.[Table: see text]